ABSTRACT
Leptin plays an essential role in the neuroendocrine regulation of obesity. It is now well established that leptin enters the brain from blood by a saturable transport system. Although it is known that perivascular astrocytes play important roles in nutrient transport across the blood-brain barrier (BBB) in general, it is not clear how astrocytes aff ect leptin transport specifi cally. Th e signifi cance of astrocyticendothelial interactions in leptin transport is emphasized by two novel fi ndings in our laboratory: (1) astrocytes show region-specifi c expression of leptin receptors (ObR); (2) mouse models of adult-onset obesity are associated with astrogliosis and up-regulation of astrocytic ObR in the hypothalamus. Th ese key fi ndings challenge the neuronal dogma in the leptin fi eld. It is possible that the glial ObR is more important in energy homeostasis once obesity is full-blown. Here we review early evidence that astrocytic ObR is involved in leptin transport, leptin signaling, obesity, and neonatal development. Th e results indicate that astrocytic ObR shows an opposing eff ect on neuronal ObR and functions as a negative regulator in energy balance. Astrocytes may determine the overall CNS actions of leptin not only by modulating the amount of leptin relayed to neurons, but also by generation of astrocytic factors. In this way, astrocytes should be considered essential functional components of the BBB that regulate leptin transport. Th e novel role of astrocytic ObR is providing new directions in the regulation of neuroendocrine disturbances related to obesity.
